The present invention relates to an implant for application in bone, for example the jaw bone, primarily of the human body. The implant comprises a unit which can be applied in the bone in question and which is made of biocompatible material, preferably titanium. At least on its surface parts cooperating with the bone, the unit is provided with a coating (or coatings) as will be described below. The invention also relates to a method for producing such an implant and to the use of such an implant.
It is already known to coat implants with films or layers on those parts which are directed towards the bone in question, for example the jaw bone. The coating is intended to initiate and stimulate bone growth where the implant has been implanted or screwed into place. It is known to use hydroxyapatite or HA in the coating. The said HA can be produced by various methods, of which one advantageous method has been found to be a method called RF sputtering, with subsequent heat treatment. It is known to use calcium phosphate compounds to achieve different release times during which the agent migrates from the layer to the surrounding bone material/jaw bone material, using different degrees of crystallization. The higher the degree of crystallization, the longer the release time, and vice versa.
Reference may be made to WO 98/48862 from the same Applicant as in the present case. The said publication gives examples of methods for applying layers of this type, and layer structures which are applicable in the present invention.
Reference may be made in purely general terms to WO 88/08460 and WO 94/25637. Reference is also made to the publications xe2x80x9cBiomaterials, Volume 17, No. 4, 1996, K. Van Dijk et al., Influence of annealing temperature on RF magnetron sputtered calcium phosphate coatings, page 405 to page 410xe2x80x9d and xe2x80x9cJournal of Biomedical Materials Research, Volume 28, 1994, J. G. C. Wolke et al., Study of the surface characteristics of magnetron-sputter calcium phosphate coatings, page 1477 to page 1484xe2x80x9d and xe2x80x9cPhosphorus Research Bulletin, Volume 6, 1996, Kimihiro Yamashita et al., Bone-Like Apatite Coating of Alumina and Zirconia by RF-Magnetron Sputtering, page 123 to page 126xe2x80x9d.
In connection with titanium implants, it is also known to arrange thick, porous titanium oxide layers which are used as depots for, inter alia, bone-growth-stimulating agents/substances (TS). In this connection, reference may be made to Swedish Patent Application No. 99 01971-3 filed on the same day and by the same Applicant, and which starts from the known arrangements according to the publications xe2x80x9cJournal of Biomedical Materials Research, by Dann et al., Gentamicin sulfate attachment and release from anodized TI-6A1-4V orthopedic materials, Vol. 27, 895-900 (1993)xe2x80x9d and xe2x80x9cJournal of Biomedical Materials Research, by Hitoshi Ishizawa and Makoto Ogino, Formation and characterization of anodic titanium oxide films containing Ca and P, Vol. 29, 65-72 (1995)xe2x80x9d.
Reference is made in purely general terms to U.S. Pat. Nos. 4,330,891 and 5,354,390.
At the present time, considerable efforts are being made to further develop and refine the implants, methods and uses in question here. Particularly in the case of a bone/jaw bone in which it is not entirely certain that the implant will incorporate in the bone, it is preferable to be able to call upon and use all the possibilities at present available in the areas in question, inter alia the dental area. The invention aims to solve this problem, among others.
There is a need to be able to control more exactly the release times for the transfer of the agents/substances from the implant layer to the surrounding bone tissue. Thus, for example, it may be necessary to achieve a better controlled release function during a defined or optimum time for the agents or the substances. The invention solves this problem too.
In certain cases, it is preferable for the implant surface cooperating with the bone structure to still have the prescribed degree of fineness even after the coating or coatings have been applied, in order, in certain implant cases, to be able to maintain relatively small tightening forces/screwing forces, for example for a tooth implant in a hole in the jaw bone. The invention solves this problem too.
Using a relatively coarse porosity can increase the tightening force considerably, which may be advantageous in certain cases but which should be avoided in other cases, especially in connection with hard bones. It may be noted here that improved healing processes in soft bones are needed. The invention solves this problem too.
It is also preferable to be able to use proven methods for producing the relevant type of implant despite the fact that the implant has better properties from the medical point of view. The invention solves this problem too.
It is often necessary to be able to accelerate the healing time for an implant. This can be controlled by suitable choice of coating or coatings. There are also problems in being able to correctly balance the initial bone growth stimulation and the long-term maintenance of the established bone growth. If bone growth is too rapid, this may give rise to bone fractures and other complications in bone growth. A long-term stimulation or the maintenance of bone growth are important for an implant which is to function for a long time or for many years without the implant needing to be changed. The invention solves this problem too.
In accordance with the invention, a bone-growth-stimulating substance or agent, here called TS, is to be used. Examples which may be mentioned are those substances belonging to the superfamily TGF-xcex2, for example BMP (Bone Morphogenetic Proteins). There may be problems in preventing the said rapid release of the TS in question. It is also preferable to be able to obtain a functionally reliable support for TS upon application to an implant surface which from the outset is amorphous or heat-treated and partially crystalline. The invention solves this problem too.
There is also a need to have access to a wider range and choice of implant types which will be able to satisfy different applications on the market, cf. implants for soft bone and hard bone, etc. The invention solves this problem too.
The feature which can principally be regarded as characterizing an implant according to the invention is that the coating or coatings comprise a CaP coating with added TS. (CaP=calcium phosphate, and TS=growth-stimulating substance).
In embodiments of the inventive concept, the time for the said agent in the said coating or coatings to be released to the surrounding bone or tissue is chosen by setting the release time for CaP and the release time for TS in relation to each other. The release time for CaP is chosen with the aid of the degree of crystallization in CaP. The total release time can be chosen within the range from a few days to several months. In one embodiment, TS is applied on top of CaP. In one embodiment, the CaP coating can have a thickness in the range of between a few angstroms and 10 xcexcm. In another illustrative embodiment, values in the range of between 0.1 xcexcm and 20 xcexcm can be used. All those areas of the said unit which cooperate with or are facing the bone material are preferably coated with the coating or layer in question. Each TS layer can have a thickness in the range of between a few angstroms and 1 xcexcm.
In one embodiment, the coating or coatings comprise one or more layers of calcium phosphate compounds and one or more layers of bone-growth-stimulating substance. Agents of the release-retarding type, for example hyaluronic acid, can be interleaved with the said layers. In a further illustrative embodiment, one or more layers of CaP can have a high degree of crystallization, for example 75-100%, which means that the layer or layers have the principal role of functioning as supports for the layer or layers of TS and possibly the release-retarding agent or agents. In a further embodiment, one or more layers of CaP can have a low or medium-high degree of crystallization, for example a degree of crystallization of between slightly over 0% and 75%, which means that the layer or layers exert a support function for TS, and possibly layers of release-retarding agents are included in the bone-growth-stimulating function. The layer or layers of CaP are preferably applied nearest to or on the actual surfaces of the implant. One or more layers of TS can be applied in turn on the last-mentioned layer or on the outer of the last-mentioned layers. In the case with two or more layers of TS, layers or agents with a release-retarding function are arranged between or outside the TS layers. At least the layer or layers of TS with possible release-retarding agent can be released with components occurring naturally in the bone and/or the tissue. The said layers and possible release-retarding agents are arranged or chosen to generate bone formation around the implant, without risk of excessively rapid bone build-up and bone fracture tendencies or other complications in the bone. The said layers and possible release-retarding agents can also be arranged to effect an initially optimum bone structure around the implant in combination with long-term (over several months) bone growth or bone-growth-stimulating function. In one embodiment, one or more CaP layers consist of hydroxyapatite or HA, and one or more layers of the bone-growth-stimulating substance consist of BMP. The release-retarding agent can have a thickness of about 0.1-1.0 xcexcm.
A method according to the invention can principally be regarded as being characterized by the fact that the said parts of the unit or the whole unit are/is coated with CaP which can be given a defined degree of crystallization by heat treatment, and TS.
CaP is preferably first applied and heat-treated, after which TS is added, for example by means of the unit, or its relevant parts to be provided with coating, being dipped in a bath of TS. Alternatively, TS can be dropped or painted onto the implant.
In a preferred embodiment, in the case where there are several TS layers, the first layer is obtained by immersing in or dropping on or painting on a TS solution with a chosen concentration. The second layer is obtained, after drying of the first layer, by dropping on or painting on of a TS solution with the chosen concentration or a second concentration which differs from the first concentration. A possible third layer is obtained, after drying of the second layer, by dropping on or painting on a TS solution with a concentration which is the same as or differs from the previously mentioned concentrations, etc. Release-retarding agents can be applied, for example by painting, on the respective dried layer. The CaP layer can be applied by so-called sputtering of CaP substance onto one or more implant surfaces which can be amorphous or heat-treated and thus crystalline. The CaP layer can be made with depressions which facilitate the holding of the outlying TS layer. Such an implant with layers of CaP and outer-lying TS layers is applied in a threaded hole in the jaw bone or equivalent in one proposed embodiment. Application methods for TS other than those mentioned can be used, for example spraying. A layer with a very high concentration of BMP can also be used.
A use, according to the invention, of the implant of the type in question is characterized essentially in that CaP and TS are used in the said coating or coatings.
The invention makes two-fold use of substances which are known per se, which have bone-growth-stimulating properties and which at least in part are already naturally present in the human body. The use of porous oxide layers in the actual implant material as a depot for growth-stimulating substance or substances has forced the skilled person away from proposals in accordance with the present invention, principally on account of the fact that in certain cases the tightening force for the implant in bone provided with holes has had to be increased. This is not in itself a disadvantage if the total range which is to satisfy different requirements on the market is considered. The release times can, according to the invention, be chosen with great precision. The TS applied on top of the CaP coating often has greater volatility than CaP. In this way, TS can provide the surrounding jaw bone with a bone-growth-stimulating function in an initial stage, which function is gradually overtaken by the CaP coating. In one illustrative embodiment, one and the same implant serves two tissue sites located at a distance from each other.